Advertisement

Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders

  • Semra Ulusoy Kaymak
  • Başaran Demir
  • Senem Şentürk
  • Ilkan Tatar
  • M. Mustafa Aldur
  • Berna Uluğ
Original Paper

Abstract

The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

Keywords

Glucocorticoids Hippocampus Magnetic resonance imaging Major depressive disorder Neurocognitive dysfunction 

Notes

Acknowledgments

This study was supported by a Grant from the Scientific Research Unit of Hacettepe University (Project No: 0302101013) and Research Project Award of Psychiatric Association of Turkey (Spring Symposia VIII). The authors would like to thank Dr. John T. O’Brien and Dr. Mr. Adrian Lloyd for their valuable contributions.

References

  1. 1.
    Aboitiz F (1992) Brain connections: interhemispheric fiber systems and anatomical brain asymmetries in humans. Biol Res 25:51–61PubMedGoogle Scholar
  2. 2.
    Bell-McGinty S, Butters MA, Meltzer CC, Greer PJ, Reynold CF 3rd, Becker JT (2002) Brain morphometric abnormalities in geriatric depression. Am J Psychiatry 159:1424–1427CrossRefPubMedGoogle Scholar
  3. 3.
    Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157:115–118CrossRefPubMedGoogle Scholar
  4. 4.
    Caetano SC, Hatch JP, Brambilla P, Sassi RB, Nicoletti N, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC (2004) Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Res 132:141–147CrossRefPubMedGoogle Scholar
  5. 5.
    Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161:598–607CrossRefPubMedGoogle Scholar
  6. 6.
    Carrol BJ (1982) The dexamethasone supression test for melancholia. Br J Psychiatry 140:292–304CrossRefGoogle Scholar
  7. 7.
    Chapman JP, Chapman IJ (1987) Handedness of hypotlletically psychosis-prone subjects. J Abnonn Psychol 96:89–93CrossRefGoogle Scholar
  8. 8.
    Colla M, Kronenberg G, Deuchle M, Meichel K, Hagen T, Bohrer M, Heuser I (2007) Hippocampal volume reduction and HPA-system activity in major depression. J Psychiatr Res 41:553–560CrossRefPubMedGoogle Scholar
  9. 9.
    Cyranowski JM, Frank E, Young E, Shear MK (2000) Adolescant onset of the gender difference in lifetime rates of major depression: a theoretical model. Arch Gen Psychiatry 57:21–27CrossRefPubMedGoogle Scholar
  10. 10.
    Czeh B, Michaelis T, Watanabe T, Frahm J, de Biumuı G, van Kampen M, Bartalomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98:12796–12801CrossRefPubMedGoogle Scholar
  11. 11.
    Czeh B, Lucassen PJ (2007) What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci 257:250–260CrossRefPubMedGoogle Scholar
  12. 12.
    Dehaene S, Changeux JP (1991) Wisconsin Card Sorting Test: theoretical analysis and modeling in a neuronal network. Cereb Cortex 1:62–79CrossRefPubMedGoogle Scholar
  13. 13.
    Ehnvall A, Sjögren M, Zachrisson OC, Agren H (2004) HPA axis activation determined by the CRH challenge test in patients with few versus multiple episodes of treatment-refractory depression. Eur Arch Psychiatry Clin Neurosci 254:349–355CrossRefPubMedGoogle Scholar
  14. 14.
    First RLS, Gibbon M, Williams JBW (1995) Structured clinical ınterview of DSM IV axis I disorders. New York State Psychiatric Institute: Biometrics Research Department, New YorkGoogle Scholar
  15. 15.
    Frodl T, Meisenzahl E, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller H (2002) Hippocampal change in patients with a first episode of major depression. Am J Psychiatry 159:1112–1118CrossRefPubMedGoogle Scholar
  16. 16.
    Frodl T, Meisenzahl EM, Zill P, Baghai T, Rujescu D, Leinsinger G, Bottlender R, Schule C, Zwanzger P, Engel RR, Rupprecht R, Bondy B, Reiser M, Moller HJ (2004) Reduced hippocampal volumes associated with the long variant of the serotonin transporter polimorphism in major depression. Arch Gen Psychiatry 61:177–183CrossRefPubMedGoogle Scholar
  17. 17.
    Hamilton M (1967) Development of a rating scale: for primary depressive illness. Br J Soc Clin Psychol 6:278–296PubMedGoogle Scholar
  18. 18.
    Heaton RK (1981) Wisconsin Card Sorting Test Manual. Psychologycal Assessment Resources, OdessaGoogle Scholar
  19. 19.
    Janssen J, Hulshoff Pol HE, Lampe IK, Schnack HG, de Leeuw FE, Kahn RS, Heeren TJ (2004) Hippocampal changes and white matter lesions in early-onset depression. Biol Psychiatry 56:825–831CrossRefPubMedGoogle Scholar
  20. 20.
    Joffe RT, Gatt JM, Kemp AH, Grieve S, Dobson-Stone C, Kuan SA, Schofield PR, Gordon E, Williams LM (2009) Brain-derived neurotrophic factor Val66Met polymorphism, the five-factor model of personality and hippocampal volume: implications for depressive illness. Hum Brain Mapp 30(4):1246–1256CrossRefPubMedGoogle Scholar
  21. 21.
    Kessler RC, McGonagle KA, Swart M, Blazer DG, Nelson CB (1993) Sex and depression in the National Comorbiditty Survey, I: lifetime prevalance, chronicity and recurrence. J Affect Disord 29:85–96CrossRefPubMedGoogle Scholar
  22. 22.
    Kirschbaum C, Pirke KM, Hellhammer DH (1993) The ‘Trier Social Stress Test’ a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81CrossRefPubMedGoogle Scholar
  23. 23.
    Klempin F, Kempermann G (2007) Adult hippocampal neurogenesis and aging. Eur Arch Psychiatry Clin Neurosci 257:271–280CrossRefPubMedGoogle Scholar
  24. 24.
    Kumsta R, Entringer S, Koper JW, van Rossum EF, Hellhammer DH, Wüst S (2007) Sex-specific associations between common glucocorticoid receptor gene variants and hypothalamus–pituitary–adrenal axis responses to psychosocial stress. Biol Psychiatry 62:863–869CrossRefPubMedGoogle Scholar
  25. 25.
    MacQueen GM, Campbell S, McEwen BS, Macdonald C, Amano S, Joffe RT, Nahmias C, Young T (2003) Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 100:1387–1392CrossRefPubMedGoogle Scholar
  26. 26.
    Mason BL, Pariante CM (2006) The effects of antidepressants on the hypothalamic–pituitary–adrenal axis. Drug News Perspect 19:603–608CrossRefPubMedGoogle Scholar
  27. 27.
    Nalcaci E, Kalaycioglu C, Gunes E, Cicek M (2002) Reliability and validity of a handedness questionnaire. Turk Psikiyatri Derg 13:99–106PubMedGoogle Scholar
  28. 28.
    O’Brien JT, Lloyd A, McKeith I, Gholkar A, Ferrier N (2004) A longitudinal study of hippocampal volume, cortisol levels and cognition in older depressed subjects. Am J Psychiatry 161:2081–2090CrossRefPubMedGoogle Scholar
  29. 29.
    Reitan R (1955) The relation of the Trail Making Test to organic brain damage. J Consult Psychol 193:393–394CrossRefGoogle Scholar
  30. 30.
    Sapolsky RM (1986) Glucocorticoid toxicity in the hippocampus: reversal by supplementation with brain fuels. J Neurosci 6:2240–2244PubMedGoogle Scholar
  31. 31.
    Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuro-psychiatric disorders. Arch Gen Psychiatry 57:925–935CrossRefPubMedGoogle Scholar
  32. 32.
    Shah BJ, Ebmeier KP, Glabus MF, Goodwin GM (1998) Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psychiatry 172:527–532CrossRefPubMedGoogle Scholar
  33. 33.
    Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D, Ebstein RP, Kaitz M (2009) BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions. Psychoneuroendocrinology 34:382–388CrossRefPubMedGoogle Scholar
  34. 34.
    Sheline YI, Wang P, Gado M, Csernansky J, Vannier M (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93:3908–3913CrossRefPubMedGoogle Scholar
  35. 35.
    Sheline YI, Sanghavi M, Mintun M, Gado M (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19:5034–5043PubMedGoogle Scholar
  36. 36.
    Sheline YI, Gado M, Kraemer H (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160:1516–1518CrossRefPubMedGoogle Scholar
  37. 37.
    Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, Blitchington TF, MacFall JR, Krishnan KR (2000) Hippocampal volume in geriatric depression. Biol Psychiatry 48:301–309CrossRefPubMedGoogle Scholar
  38. 38.
    Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, Krishnan RR (2005) Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late life depression. Arch Gen Psychiatry 62:537–544CrossRefPubMedGoogle Scholar
  39. 39.
    Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161:1957–1966CrossRefPubMedGoogle Scholar
  40. 40.
    Vythilingam M, Vermetten E, Anderson GM, Luckenbaugh D, Anderson E, Snow J, Staib LH, Charney DS, Bremner DJ (2004) Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 56:101–112CrossRefPubMedGoogle Scholar
  41. 41.
    Wechsler D (1987) Wechsler Memory Scale Revised (manual). Psychological Corporation, San AntonioGoogle Scholar
  42. 42.
    World Health Organization (1993) WHO/MNH Battery of cognitive assessment instrumentre pilot battery. WHO, GenevaGoogle Scholar
  43. 43.
    Yu S, Holsboer F, Almeida OF (2008) Neuronal actions of glucocorticoids: focus on depression. J Steroid Biochem Mol Biol 108:300–309CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Semra Ulusoy Kaymak
    • 1
  • Başaran Demir
    • 2
  • Senem Şentürk
    • 3
  • Ilkan Tatar
    • 4
  • M. Mustafa Aldur
    • 4
  • Berna Uluğ
    • 2
  1. 1.Ankara Oncology Training and Research Hospital Psychiatry ClinicAnkaraTurkey
  2. 2.Department of Psychiatry, Faculty of MedicineUniversity of HacettepeAnkaraTurkey
  3. 3.Department of Radiology, Faculty of MedicineUniversity of HacettepeAnkaraTurkey
  4. 4.Department of Anatomy, Faculty of MedicineUniversity of HacettepeAnkaraTurkey

Personalised recommendations